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Biomedical subjects

R L Winslow

Publications and source records attributed to R L Winslow.

At least 37 records · Page 2Linked to original sources
PubMed1994

A model of selective processing of auditory-nerve inputs by stellate cells of the antero-ventral cochlear nucleus.

Stellate cells in the cat antero-ventral cochlear nucleus (AVCN) maintain a robust rate-place representation of vowel spectra over a wide range of stimulus levels. This rate-place representation resembles that of low threshold, high spontaneous rate (SR) auditory nerve fibers (ANFs) at low stimulus levels, and that of high threshold, low-medium SR ANFs at high stimulus levels. One hypothesis accounting for this phenomenon is that AVCN stellate cells selectively process inputs from different SR population of ANFs in a level-dependent fashion. In this paper, we investigate a neural mechanism that can support selective processing of ANF inputs by stellate cells. We study a physiologically detailed compartmental model of stellate cells. The model reproduces PST histograms and rate-versus-level functions measured in real cells. These results indicate that simple and plausible distribution patterns of excitatory and inhibitory inputs within the stellate cell dendritic tree can support level dependent selective processing. Factors affecting selective processing are identified. This study thus represents a first step towards the development of a computational model of the AVCN stellate cell receptive field.

Animals↗
PubMed1994

Effects of gap junction conductance on dynamics of sinoatrial node cells: two-cell and large-scale network models.

A computational model of single rabbit sinoatrial (SA) node cells has been revised to fit data on regional variation of rabbit SA node cell oscillation properties. The revised model simulates differences in oscillation frequency, maximum diastolic potential, overshoot potential, and peak upstroke velocity observed in cells from different regions of the node. Dynamic properties of electrically coupled cells, each with different intrinsic oscillation frequency, are studied as a function of coupling conductance. Simulation results demonstrate at least four distinct regimes of behavior as coupling conductance is varied: a) independent oscillation (Gc < 1 pS); b) complex oscillation (1 < or = Gc < 220 pS); c) frequency, but not waveform entrainment (Gc > or = 220 pS); and d) frequency and waveform entrainment (Gc > or = 50 nS). The conductance of single cardiac myocyte gap junction channels is about 50 pS. These simulations therefore show that very few gap junction channels between each cell are required for frequency entrainment. Analyses of large-scale SA node network models implemented on the Connection Machine CM-200 supercomputer indicate that frequency entrainment of large networks is also supported by a small number of gap junction channels between neighboring cells.

Algorithms↗
PubMed1994

Chronic monitoring of cardiovascular function in the conscious guinea pig using radio-telemetry.

An implantable radio-telemetry device for chronic monitoring of arterial pressure and heart rate in the conscious guinea pig was validated against measurements using an exteriorized, indwelling catheter. There were no significant differences between simultaneous measurements in animals instrumented with both the telemetry system and the conventional catheter (implanted 24 hrs prior to comparisons) in response to a variety of vasoactive agents. The device was shown to be accurate up to 3 weeks after implantation (longest time point tested). Resting pressures and heart rates in the telemetered guinea pig were stable in 100% of the animals tested. In contrast, animals instrumented with only exteriorized catheters showed a significant decline in pressure by 8 days after surgery and a 39% attrition rate due to loss of catheter patency. Performance of the telemetric device was examined in both normal and sodium-deficient animals, since the latter is a useful normotensive model in which blood pressure is rendered highly renin-dependent for evaluating the efficacy of potential antihypertensive agents that target the renin-angiotensin system. The telemetered guinea pig is an appropriate model for assessing responses to chronic exposure of cardiovascular agents.

Animals↗
PubMed1993

Generation and propagation of ectopic beats induced by spatially localized Na-K pump inhibition in atrial network models.

A biophysically detailed two-dimensional network model of the cardiac atrium has been implemented on the Thinking Machines massively parallel CM-5 supercomputer. The model is used to study the effects of spatially localized inhibition of the Na-K pump. Na overloading produced by pump inhibition can induce spontaneous, propagating ectopic beats within the network. At a cell-to-cell coupling value yielding a realistic plane wave conduction velocity of 0.6 m s-1, pump inhibition in roughly 1000 cells can induce propagating ectopic beats in a 512 x 512 lattice of cells.

Action Potentials↗
PubMed1990

Bifurcation analysis of nonlinear retinal horizontal cell models. II. Network properties.

1. We have previously presented a model of horizontal-cell soma isolated from fish retina. The model consists of a synaptic conductance representing input from photoreceptors in parallel with voltage-dependent membrane currents. Membrane-current models are based on I-V curves measured in isolated fish horizontal cells. Bifurcation theory was used to analyze model properties. The major findings of this study were 1) the inward Ca2+ current must be inactivated to account for horizontal-cell resting potentials and hyperpolarizing responses to light stimuli in a background of dark, and 2) the synaptic conductance controls the bifurcation structure of the model, with bistable behavior occurring at small and monostable behavior occurring at larger values of the synaptic conductance. The synaptic conductance at the point of transition from bistable to monostable behavior corresponds to the activation of as few as 100 synaptic channels. Thus tonic synaptic input from photoreceptors and inactivation of the inward Ca2+ current act to "linearize" responses of isolated horizontal-cell models. 2. The model described in this paper extends these analyses to large networks of horizontal cells in which each cell is coupled resistively to its nearest neighbors and is modeled with the use of the full complement of nonlinear membrane currents. Network responses to arbitrary patterns of conductance change (simulating inputs from photoreceptors), current-, or voltage-clamp stimuli are computed using the Newton iteration. The Newton descent direction is computed using either conjugate gradient (CG) or preconditioned CG algorithms. 3. An analysis of network stability properties is performed. Network I-V curves are computed by voltage-clamping the center node and computing the current required to maintain the clamp voltage. Computations are performed on networks of model cells in which the Ca2+ current is fully activated and the synaptic conductance is zero, thus making each cell as nonlinear as possible. Coupling conductance values slightly greater than 100 pS provide a current shunt sufficient to prevent the generation of Ca2+ action potentials in the network. This coupling conductance corresponds to the conductance of as few as two gap-junction channels and is more than two orders of magnitude less than the coupling known to exist between pairs of cultured horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

A theoretical and experimental study of the effects of non-uniform membrane resistance on the shape of single-cell charging curves.

The isolated Muller glial cell of the neotenous tiger salamander retina is used as an experimental model for studying the effects of non-uniform membrane conductance on the shape of charging curves in response to step current inputs. A simple cable model of the Muller cell is formulated and used to interpret the experimental data. The Muller cell model is completely described by three parameters: (a) electrotonic length L; (b) the membrane time constant tau m; and (c) the percentage of the total membrane conductance accounted for by the endfoot S. Model analysis indicates that increasing S produces monotonic decreases in the rise time of charging curves. This effect is greatest when L is small. In such cases charging curve rise time can be substantially faster than that of a semi-infinite cable. When S greater than 0, the first time constant obtained by fitting the late exponential tail of the charging curve is not the membrane time constant (as is the case when S = 0), but is instead an equalizing time constant equal to the membrane time constant times a scale factor in the range of 0 to 1. This scaling factor becomes quite small as S approaches 100%. We describe a convergent numerical procedure for generating unique estimates of all three model parameters from charging curves. Application of the algorithm to experimentally measured Muller cell charging curves confirms Newman's finding that a large fraction of membrane conductance in these cells is accounted for by the endfoot (greater than 90%). The model prediction that charging curve rise time may be substantially faster than that of the semi-infinite cable when S greater than 0 is also confirmed. The error that results from misinterpreting the first equalizing time constant tau l as the membrane time constant tau m can have a significant effect on estimates of specific membrane resistance and capacitance. The algorithm described in this paper provides a means for obtaining direct estimates of the membrane time constant and will make possible more accurate estimates of specific membrane resistance and capacitance in Muller glial cells. The fact that the estimation procedure is based on a simple electrophysiological measurement suggests that it may be useful for studying asymmetry of membrane conductance in glial and neural elements of the intact nervous system.

Animals↗
PubMed1989

A computational model for rate-level functions from cat auditory-nerve fibers.

A computationally tractable form of the rate-level model proposed by Sachs and Abbas (1974) is presented. The first stage of the model is a compressive nonlinearity whose input-output function is chosen to reflect current data on basilar-membrane displacement. The output of this nonlinearity is converted to driven discharge rate by the saturating nonlinearity originally used by Sachs and Abbas (1974). In fitting the model to data four model parameters are chosen to minimize the mean squared error between rate functions generated by the model and the data. With parameters chosen in this way, the model provides good fits to the range of rate-level shapes from flat saturations to sloping saturations. One important parameter in the model is the 'threshold for compression'. For low- and medium-spontaneous rate fibers with similar best frequencies (BFs), the minimum mean squared error compression threshold is roughly constant at about 30 dB above the thresholds of the most sensitive (high-spontaneous rate) fibers at that BF.

Animals↗
PubMed1989

Functional role of spines in the retinal horizontal cell network.

Compartmental models derived from serial electron-microscopic reconstructions of horizontal cell processes entering cone pedicles and rod spherules are used to show that these processes have the morphological and electrical characteristics of dendritic spines. Properties of these spines are incorporated into a distributed model of the horizontal cell network. Expressions relating the magnitude of conductance changes applied at the spine heads to hyperpolarization of cells within the network are derived. Model analyses show that spine properties play a critical role in determining network responses. Specifically, increasing spine stem resistance increases the network input resistance and space constant, hyperpolarizes the resting potential, decreases response to full-field light stimuli, and increases response to small light spots. Increasing spine-stem resistance also decouples potential at the spine head from potential at the cell body. This result suggests that the location of feedback neurotransmitter release sites (e.g., at the spine heads versus the cell body) may have a profound influence on properties of horizontal cell inhibition of cone response. Because of these important functional consequences, structurally realistic models of the horizontal cell network must incorporate spine properties.

Animals↗
PubMed1989

Bifurcation analysis of nonlinear retinal horizontal cell models. I. Properties of isolated cells.

1. Bifurcation theory is used to study properties of nonlinear analytical and computational models of isolated retinal horizontal cells. The analytical model is based on the published data of Shingai and Christensen describing steady-state I-V characteristics of horizontal cells isolated from catfish (Ictalurus punctatus) retina. The computational model is based on I-V characteristics of distinct macroscopic membrane currents observed in horizontal cells isolated from goldfish (Carassius auratus) retina. Slow-model dynamics are analyzed assuming that excitatory processes occur rapidly with respect to the time course of inactivation of the inward Ca2+ and outward K+ currents. 2. A global bifurcation diagram plotting the location and stability properties of critical points as a function of photoreceptor-evoked horizontal-cell postsynaptic membrane conductance Gsyn is derived for the analytical model. The automated bifurcation analysis software AUTO is used to compute global bifurcation diagrams for the computational model. Bifurcation diagrams exhibit a bistable regime at small Gsyn values characterized by two stable and one unstable critical point and a monostable regime at larger Gsyn values characterized by a single globally attracting stable critical point. The transition between bistable and monostable behavior occurs at a Gsyn value of roughly 0.9 nS for the computational model and 1.7 nS for the analytical model. Estimates of horizontal-cell glutamate-channel conductance suggest that this transition corresponds to the activation of as few as 400-700 glutamate channels. Dark-evoked release of neurotransmitter from photoreceptors may therefore set horizontal-cell synaptic conductance Gsyn to a value within the monostable regime. 3. Photoreceptor-evoked horizontal-cell membrane conductance, total Ca2+ channel conductance, and inactivation of the inward Ca2+ current are shown to be the major factors controlling the bifurcation structure of the computational model. Inactivation of the inward Ca2+ current is required to account for the dark resting potential of horizontal cells as well as light-evoked hyperpolarizing responses. Inactivation of the outward K+ current has little effect on model properties. 4. Isolated horizontal cells generate Ca2+ action potentials whereas cells in the intact retina normally do not. Simple procedures for modeling the slow dynamics of isolated horizontal-cell Ca2+ action potentials are described.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1988

Single-tone intensity discrimination based on auditory-nerve rate responses in backgrounds of quiet, noise, and with stimulation of the crossed olivocochlear bundle.

We use simple statistical models of the firing patterns of high, medium, and low spontaneous rate auditory-nerve fibers to study mechanisms which determine the overall dynamic range of the auditory periphery. The models relate experimentally measured rate response properties of fibers with best frequency (BF) near 8.0 kHz to their ability to encode changes in BF tone level by changes in discharge rate in backgrounds of quiet and noise, with and without electrical stimulation of the crossed olivocochlear bundle (COCB). Application of the models to the BF tone rate responses of auditory-nerve fibers in backgrounds of quiet shows that optimum processing of the rate responses of fibers with BF near 8.0 kHz yields performance in the intensity discrimination task meeting or exceeding that of human subjects over an 80 dB range of levels. By defining a statistical measure of dynamic range, we confirm the results of Costalupes et al. (1984) demonstrating that masking noise shifts the dynamic range of auditory-nerve fibers to higher stimulus levels, thus preventing rate saturation. However, model analysis shows that masking noise also produces large reductions of dynamic range as well as large increases in the minimum intensity difference that can be encoded by the rate responses of single and ensembles of fibers. Electrical stimulation of the COCB can restore auditory-nerve fiber dynamic range and sensitivity to changes in BF tone level in noise backgrounds, in some cases to roughly that observed in backgrounds of quiet.

Animals↗
PubMed1987

Effect of electrical stimulation of the crossed olivocochlear bundle on auditory nerve response to tones in noise.

The discharge rates of single auditory-nerve fibers responding to best-frequency (BF) tones of varying level presented simultaneously with fixed level broadband noise were recorded with and without electrical stimulation of the crossed olivocochlear bundle (COCB). In the absence of COCB stimulation, monotonic increases in noise level produce monotonic increases in the low-level noise-driven response rate of auditory nerve fibers. As a result of adaptation, these increases in noise-driven response rate produce monotonic decreases in saturation discharge rate. At high noise levels, these compressive effects may eliminate the differential rate response of auditory nerve fibers to BF tones. COCB stimulation can restore this differential rate response by producing large decreases in noise-driven response rate and large increases in saturation discharge rate. In backgrounds of quiet, COCB stimulation is known to shift the dynamic range of single auditory nerve fiber BF tone responses to higher stimulus levels. In the presence of background noise, COCB stimulation produces upward shift of dynamic range, which decreases with increasing noise level. At high noise levels, COCB-induced decompression of rate-level functions may occur with little or no dynamic range shift. This enables auditory nerve fibers to signal changes in tone level with changes in discharge rate at lower signal-to-noise ratios than would be possible otherwise. Broadband noise also produces upward shift of the dynamic range of single auditory nerve fiber BF tone response. Noise-induced dynamic range shift of BF tone response was measured as a function of noise level with and without COCB stimulation. COCB stimulation elevates the threshold of noise-induced dynamic range shift. This shift is thought to result from two-tone rate suppression. Increases in the threshold of noise-induced shift due to COCB stimulation therefore suggests an interaction between the mechanism of two-tone rate suppression and the mechanism by which COCB stimulation produces dynamic range shift. These interactions were further investigated by recording auditory nerve fiber rate responses to fixed-level BF excitor tones presented simultaneously with fixed-frequency variable level suppressor tones. Rate responses were recorded with and without COCB stimulation. Experimental results were quantified using a phenomenological model of two-tone rate suppression presented by Sachs and Abbas.

Acoustic Stimulation↗
PubMed1985

Retinal complications following YAG laser capsulotomy.

Eighteen patients (19 eyes) developed retinal complications following YAG laser capsulotomy. Complications included one retinal flap tear, two macular holes, six eyes with cystoid macular edema, and ten retinal detachments. The retinal complications resulted from opening the capsule and were not a specific complication of the YAG laser.

Aged↗
PubMed1981

Pseudophakic flat anterior chamber following retinal detachment repair.

Flat anterior chambers were caused by varying mechanisms in 10 of 70 consecutive pseudophakic eyes operated on for retinal detachment. With iris or capsular implant fixation, three of 46 (7%) developed flat anterior chambers, and with anterior chamber lenses, the occurrence was seven of 24 (29%). Events initiating flat chambers included wound leak, pupillary block, and choroidal detachment. In eyes with flat anterior chambers, the retina could not be reattached in one case, extensive peripheral anterior synechia with persistent intraocular pressure elevation occurred in another case, and bullous keratopathy remained in two additional instances. Endothelial cell densities were obtained in eight eyes and were low on an age-related basis.

Aged↗
PubMed1980

Spontaneous vitreous hemorrhage: etiology and management.

Spontaneous vitreous hemorrhage, without trauma, accounted for 317 patients (375 eyes) seen during a four-year period from July 1, 1975, to June 30, 1979. The most common causes were proliferative diabetic retinopathy, 39.2%; retinal tear, 12.1%; posterior vitreous detachment, 12%; vein occlusion, 10.4%; retinal detachment, 6.7%; intraocular lens, 3.2%; proliferative sickle retinopathy, 1.3%; miscellaneous, 7.4%; and unknown, 6.7%. Emphasis is placed on the importance of establishing the specific cause so that specific therapy may be instituted.

Anemia, Sickle Cell↗
PubMed1978

Juvenile rhegmatogenous retinal detachment.

Between Jan 1, 1966, and June 30, 1974, 179 children, birth through 16 years of age with rhegmatogenous retinal detachments, underwent scleralbuckling procedures at Wills Eye Hospital. The detachments were associated most frequently with trauma (44%), myopia (15%), aphakia (10%), and retinopathy of prematurity (8%). Successful reattachment was achieved in 80% of the cases. Vision of 20/100 or better was present in 22% preoperatively and 58% postoperatively.

Adolescent↗
PubMed1977

Cystoid macular edema following intraocular lens implantation.

This presentation recounts the original description of CME and the more recent developments associated with intravenous fluorescein angiography in its study and diagnosis. The work of previous authors to show the incidence of CME and its possible prognosis are reviewed. Our findings in a retrospective study agree with the other authors and show that there is no particular increase in CME following intraocular lens implantation regardless of the type of surgical procedure used. It is established that vitreous loss does increase the incidence of CME. A prospective study with routine intravenous fluorescein at six weeks is presented and shows an incidence that is below that found by other authors when it was performed following routine intracapsular cataract extraction.

Cysts↗